High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome

Hantavirus pulmonary syndrome (HPS) is characterized by the rapid onset of pulmonary edema and a high case-fatality rate. Hantavirus antigens have bee n demonstrated in pulmonary capillary endothelial cells, but the mechanisms causing capillary leakage remain unclear. Immunohistochemical staining was used to enumerate cytokine-producing cells (monokines: interleukin [IL]-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor [TNF]-alpha; lymphokines: interferon-gamma, IL-2, IL-4, and TNF-beta) in tissues obtained at autopsy from subjects with HPS. High numbers of cytokine-producing cells were seen in the lung and spleen tissues of HPS patients, but only low numbers in th e livers and kidneys. A modest increase in the numbers of cytokine-producin g cells was detected in the lungs of patients who died with non-HPS acute r espiratory distress syndrome (ARDS), and very few (or no) cytokine-producin g cells were detected in the lungs of patients who died of causes other tha n ARDS, These results suggest that local cytokine production may play an im portant role in the pathogenesis of HPS.